There are over 250,000 paraplegics in the United States today. Since regeneration of the human spinal cord is abortive, a basic understanding of the mechanisms of potential growth and regenerative capacity of the vertebrate spinal cord is essential for patient management and eventual elimination of this national health problem. The morphology of the injured mammalian spinal cord will be studied with electron and light microscopy. The inability of the mammalian central nervous system to regenerate axons or axonal sprouting across the site of spinal cord lesion appears to be due to the reaction of the neurons just proximal to the site of the lesion. Following spinal cord injury, the deafferented neurons in this region undergo morphological alteration (varicosity formation on dendrites, etc.). The altered neurons proximal to the lesion site are cyclically and nonselectively reinnervated by axonal sprouts and regenerating nerve fibers which reach maximum numbers at 30 and 90 days postoperative and spontaneously degenerate to lower numbers 60 days postoperative. This reinnervation occurs on neurons with altered dendritic morphology. Depression of the neuronal reaction by protein inhibitors (puromycin) results in inhibition of the neuronal reaction due to spinal cord injury. Puromycin treatment makes deafferented motorneurons in the hemisected spinal cord resistant to change in dendritic morphology and neuronal chromatolysis. Under these conditions axonal sprouts and limited numbers of regenerating axon grow into the site of lesion. The past experiment will attempt to quantify the neuronal reaction to spinal cord injury and study the neuronal modification following administration of various protein inhibitory drugs as a mechanism for inducing spinal cord regeneration. Studies will also be carried out on lower vertebrates to assess the abiltiy of these animals to regenerate nerve fibers into new neuronal circuits which result in the return of function and compare these models of successful regenerative patterns with the inability of the mammalian central nervous system to functionally intergrate neuronal connections.